Programmed Death-Ligand 1 Expression in Non-Small Cell Lung Carcinoma Biopsies and Its Association with Tumor Infi ltrat ing Lymphocytes and the Degree of Desmoplasia.

BACKGROUND: Immunotherapy blocking the PD-1/PD-L1 signalling pathway has become a dominant treatment modality for patients with non-small cell lung carcinoma (NSCLC). Programmed death-ligand 1 (PD-L1) expression on the membrane of tumour cells and/or tumour infiltrating lymphocytes (TIL) evaluated immunohistochemically is still the only clinically validated predictive biomarker for immunotherapy, but it has its limitations. TIL in the tumour microenviroment was identified as having predictive value. We retrospectively evaluated 134 NSCLC resection specimens, and analysed the association between PD-L1 expression, the presence of TIL, and the degree of desmoplasia in tumours. MATERIAL AND METHODS: PD-L1 expression on tumour cells and TIL were evaluated immunohistochemically using the anti-PD-L1 antibody (clone 22C3) and the anti-CD3 antibody (polyclone), respectively. PD-L1 was scored using the “tumour proportion score” (TPS) system with three categories: TPS < 1%, 1-49%, and 50%. TIL were evaluated semiquantitatively using the “percentage of stromal TIL” (PST) system, and categories of PST < 10%, 10-49% and 50% were recorded. The association between PD-L1 expression in tumour cells and TIL was compared with the PST value. Statistical analysis was conducted using the Cochran-Armitage test, and a p-value < 5% was considered significant. RESULTS: PD-L1 expression was significantly higher in PST 10-49% and 50% categories than in the PST < 10% category in grade 1 and grade 2 adenocarcinomas (p = 0.008), grade 3 adenocarcinomas (p = 0.009), and squamous cell carcinomas (p = 0.028). PD-L1 expression in TIL was associated with the PST value in squamous cell carcinomas (p = 0.025) but not in adenocarcinomas. Desmoplastic tumours had particularly low TPS and PST values. CONCLUSION: PD-L1 expression in NSCLC is associated with the presence of TIL. Desmoplastic areas in tumours represent immunologically inactive tumour microenviroments. Administration of anti-PD-1/PD-L1 immunotherapy, together with agents blocking the TGF-β signalling pathway, represent a promising combinational therapy for patients with desmoplastic NSCLC. The authors declare they have no potential confl cts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 25. 11. 2019 Accepted: 8. 12. 2019.

[Lung pneumatocele in adult patient - case report]. / Plúcna pneumatokéla u dospelého pacienta - kazuistika.

Lung pneumatoceles are characterized by a thin-walled air-filled cavity present in lung parenchyma. Mostly they are the result of acute bronchopneumonia after spontaneous drainage of altered lung parenchyma with subsequent development and progression of cavities due to ventile mechanism. This disease is more prevalent in infants and young children, it is rather rare in adults. In the present case report, videothoracoscopy resection of lung pneumatocele of the right lower lobe was performed a 43-years old man. The operation was indicated for the presence of chronic persisting and progressing pneumatocele as a preventive measure of pneumatocele complications.

Induced sputum eosinophils, bronchial reactivity, and cough sensitivity in subjects with allergic rhinitis.

Some patients with allergic rhinitis and no clinical evidence of asthma exhibit bronchial hyperresponsiveness. In the present study, induced sputum and acetylcholine and capsaicin challenges were assessed in four groups of adult subjects: allergic rhinitis (AR), allergic rhinitis with lower airway symptoms (ARLA), mild stable asthma (BA), and healthy volunteers (C) to correlate lower airway inflammatory markers with bronchial and cough reactivity. Patients with AR (n = 13) and ARLA (n = 11) did not take any anti-inflammatory drugs. Those with BA (n = 9) used inhaled corticosteroids and C (n = 10) were respiratory symptoms free. The patients underwent capsaicin cough challenge and sputum induction with hypertonic saline during the first visit, and acetylcholine bronchial challenge on a separate day. We found that the percentage of eosinophils in induced sputum was significantly higher in patients with AR, ARLA, and BA than in C 14.5 +/-1.8(SE) vs. 13.5 +/-2.9 vs. 13.9 +/-4.0 vs. 3.6 +/-0.8 %, respectively (P=0.012). In contrast, acetylcholine PD(20) in patients with AR, ARLA, and BA was significantly lower than in C 5.6 +/-0.9 vs. 4.1 +/-0.4 vs. 2.8 +/-0.4 vs. 12.9 +/-2.7 mg, respectively (P=0.0001). Neither the eosinophil percentage nor PD20, nor cough sensitivity appreciably differed across the patients groups. Sputum eosinophils correlated significantly with the acetylcholine PD(20) (r=0.37, P=0.016). We conclude that eosinophilic inflammation of lower airways and increased bronchial reactivity were present in adult patients with allergic rhinitis.

[Microstructure of subcutaneous lesions in juvenile hyaline fibromatosis]. / Mikrostruktúra podkozných lézií juvenilnej hyalínovej fibromatózy.

Juvenile hyaline fibromatosis is a rare autosomal recessive interstitial disease characterized by nodes and tumours of skin and soft tissues as well as by gingival hyperplasia. The authors described a case of 28-year-old male based on histopathological diagnosis. The patient was admitted to the hospital thrice in his life with the diagnosis of arthrogryphosis. Last time he presented with extensive secondary impetigo in extremities and pachydermia, polymalformation syndrome, multiple subcutaneous tumours, gingival hypertrophy, contractures, osteolytic lesions and positive family history. In histology, tumoriform lesions showed a structureless hyaline matrix often with chondroosseous metaplasia and calcium salts. More or less numerous cells in the matrix had a fibroblastoid appearance with eosinophilic cytoplasm, oval nuclei and frequently pericytoplasmic halo. Electron microscopy revealed dilated cisterns of rough endoplasmic reticulum and a hypertrophied Golgi apparatus. Particles representing calcium salts according to their density were rare. Immunohistochemistry of tumour cells showed vimentin, alpha-1-antichymotrypsin and alpha-1-antitrypsin. The findings concurred with the literature in which, nevertheless, the immunohistochemical picture were not mentioned.

[Juvenile hyaline fibromatosis]. / Juvenilná hyalínová fibromatóza.

BACKGROUND: Juvenile hyaline fibromatosis is a sporadic hereditary disease with autosomal recessive mode of inheritance, characterized by the presence of nodules and tumours in the skin and soft tissues and gingival hyperplasia. The majority of patients are growth retarded, suffer from joint disorders, contractures, osteolytic lesions and have a positive family history. The disease most frequently occurs in children, but may be diagnosed also in adults. Since 1873, when the disease was described by Murray, only a few cases were introduced in the literature. THE AIM AND THE BASIS OF THE STUDY: To present the clinical pattern of a patient diagnosed at the age of 28 and describe also the histopathological, immunohistological and electron-microscopic findings of excisions from the lesions. METHODS: The pathologist in cooperation with clinicians from several disciplines established the diagnosis on the basis of typical histopathological picture and additional immunohistological tests not yet introduced in the literature. RESULTS: Tumorous lesions contained hyaline structureless matrix often with chondroid or even osteoid metaplasia, calcium salts. The matrix contained numerous fibroblastoid-like cells with eosinophilic cytoplasm, oval nucleus and often pericytoplasmic halo. ELMI investigation revealed dilated cisternae of rough endoplasmic reticulum and hypertrophic Golgi apparatus. Sporadically were particles with calcium salts density detected. Immunohistochemical tests revealed the expression of vimentin, alfa1-antitrypsin and alfa1-antichymotripsin by the tumorous cells. CONCLUSION: The authors presented an extremely sporadic childhood disease in an adult. The results are in accordance with the data from the literature. Immunohistochemical picture of "cementicles" has not yet been introduced in the available literature. (Fig. 12, Ref. 25.)

Organ distribution and autoradiography after administration of 125I-16 alpha-iodo-estradiol in female rats.

Tissue distribution experiments with 125I-1 16 alpha-iodo-estradiol (Amersham) showed the highest tissue-to-blood ratio of 3 to 8 in the liver, uterus, mammary gland, ovaries and adrenals up to 2 h after the injection. Satisfactory images with a simple autoradiographical techniques according to Stumpf [1971] have been achieved at 2 h after the injection of drug.